Heavy metals are known to damage the nervous tissue in humans, but the molecular mechanisms of damage are unknown. The objective of this proposal is to investigate the molecular mechanisms of heavy metal-induced damage to nervous tissue using monolayer cultures of glioma and neuroblastoma (NB) cells as an experimental model. We propose to study the following: (a) Effect of methylmercuric chloride (CH3HgCl) and mercuric chloride on cyclic AMP phosphodiesterase activity in homogenates of untreated cells; (b) The reversibility of changes in gene expression induced by chronic treatment of cells with CH3HgCl; (c) Effect of glioma factors on CH3HgCl-induced damage of NB cells; (d) Effect of chronic treatment of NB cells with CH3HgCl on dopamine- and norepinephrine (NE)-sensitive adenylate cyclases; (e) Effect of ethylmercuric chlorides on glioma and NB cells for the criteria of growth inhibition and morphological differentiation; (f) Determination of the basal level of adenylate cyclase activity, cyclic AMP binding proteins and cyclic AMP phosphodiesterase activity in acutely treated cells; (g) Effect of CH3HgCl on adenosine-stimulated level of cyclic AMP in NB cells; (h) Further studies on the effect of CH3HgCl on gene expression; (i) Effect of CH2HgCl on modification of histones; (j) Development of the technique of dissociated cultures of chick embryo brain. Results may increase our understanding of the molecular mechanisms of damage of nervous tissue caused by organic mercury compounds.